[Cell-mediated immunity: Lupus and connective tissue diseases]. / Auto-immunité à médiation cellulaire : lupus et connectivités.

Lupus can present itself in a multitude of clinical and histopathological manifestations. Cutaneous lesions can be very variable either from the clinical point of view or at the microscopic scale. Signs can be specific, concerning the dermo-epidermal stage, the dermal stage or the hypodermal stage. Conversely, some manifestations can be not specific but associated to the lupus. Finally, the question of the differential diagnosis can be tricky and often requires a beam of clinical, biological and histopathological arguments.

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma with KIR3DL2 and NKp46 expression in a human immunodeficiency virus carrier.

Primary cutaneous aggressive epidermotropic T-cell lymphoma (PCAETCL) is a very rare lymphoma characterized by rapidly growing necrotic cutaneous lesions with an epidermotropic CD8+ T-cell neoplastic infiltrate observed histopathologically. It is associated with a very poor outcome, despite aggressive multi-agent chemotherapy. We report a 49-year-old human immunodeficiency virus (HIV)-infected patient who developed PCAETCL with associated marked vascular injury leading to diffuse purpuric and necrotic lesions complicated by recalcitrant hemophagocytic activation syndrome. The lymphoma strongly and diffusely expressed CD158k/KIR3DL2 at the protein and transcript level and NKp46 transcripts, in addition to CD8 and cytotoxic proteins. We observed a diffuse CD158k/KIR3DL2 protein expression in another case of PAETCL, not associated with immunodeficiency, which was used as a positive control. PCAETCL can develop in HIV-infected patients and may present in vasculitis-like fashion. The possible role of immunosuppression and/or HIV in oncogenesis can be postulated, as patients infected with HIV may develop anti-HIV cytotoxic CD8+ lymphoproliferations. The frequency of CD158k/KIR3DL2 and NKp46 expression in PCAECL remains to be studied in a series of cases, and may represent interesting targets for future treatments.

Multiple tubulovillous adenomas of the vulva.

Enteric-type lesions are rare in the female genital tract. We report the first case of multiple vulvar tubulovillous adenomas with transformation into adenocarcinoma. A 31-year-old woman presented with recurrent vulvar polypoid lesions resembling condylomas that were excised. These tumors were characterized by their tubulovillous architecture and intestinal differentiation, with columnar epithelium, goblet cells, and Paneth cells. As in their colonic counterpart, the degree of dysplasia was evaluated. The lesions consisted of 3 low-grade adenomas and 1 adenocarcinoma with superficial invasion. After 15 months, there is no sign of recurrence. The clinical presentation, pathological findings, differential diagnoses, and pathogenesis are discussed.

Clinical and histological features of fixed drug eruption: a single-centre series of 73 cases with comparison between bullous and non-bullous forms.

The clinical and pathological aspects of fixed drug eruption (FDE) have been described based on a few case series. To compare bullous FDE (BFDE) and non-bullous FDE (NBFDE) and to determine whether BFDE can be histologically distinguished from other dermatoses presenting with an apoptotic pan-epidermolysis. In this retrospective monocentre study (2005-2016), FDE was classified as BFDE or NBFDE and localized (one anatomical site) or generalized (≥ two sites; GBFDE). Clinical data were extracted from charts, and images were reviewed. Skin biopsies were analysed and compared to the clinical presentation. Three dermatopathologists, blinded to the final clinical diagnosis, evaluated a subset of BFDE cases (n = 8) and 25 biopsies of other bullous diseases known to have an epidermal necrolysis (EN)-like pattern. In total, 73 patients were included in the study. Patients with BFDE (n = 58; GBFDE n = 48) were significantly older (p < 0.001). All patients with GBFDE were hospitalized; 25 had a complication (infectious; n = 19), and eight died (median age: 80). Histology revealed spongiotic (6.7%), interface dermatitis (48.3%) and EN-like (66.3%) patterns. The EN-like pattern was more frequent in BFDE than NBFDE (74% vs 27%; p = 0.008). Melanophages (100% vs 66%; p = 0.02) and massive dermal melanosis (40% vs 4%; p = 0.0005) were more prominent in NBFDE than BFDE. BFDE could not be reliably distinguished from other bullous diseases with EN-like patterns. BFDE belongs to the spectrum of skin conditions with an EN pattern, for which the concept of acute syndrome of apoptotic pan-epidermolysis (ASAP) was previously introduced. Clinical-pathological correlation is mandatory for a diagnosis of BFDE.

Colorectal neuroendocrine carcinomas and adenocarcinomas share oncogenic pathways. A clinico-pathologic study of 12 cases.

OBJECTIVE: Neuroendocrine carcinomas (NECs) are rare neoplasms with an increasing incidence. Oncogenetic pathways of colorectal NEC are still poorly understood, and no treatment standards are available for these rare tumors. METHODS: We analyzed retrospectively the clinical records and histology of 12 patients with colorectal NEC. KRAS and BRAF mutations were investigated after the dissection of exoendocrine and neuroendocrine components. ALK alterations and EML4-ALK transcripts were detected by in-situ hybridization and determination of fusion transcripts, respectively. RESULTS: At the time of diagnosis, the mean age of the patients was 60 years (40-79) and 10 patients had synchronous metastases. A transient response occurred in two patients and one patient treated with cisplatin-etoposide or fluoropyrimidine-oxaliplatin, respectively. Tumor progression-related death occurred in 11 of 12 patients. Ten tumors contained an exocrine component, accounting for 5-70% of the tumor, and the other two contained an amphicrine component. BRAF/KRAS mutations were found in six of 10 tumors, corresponding to BRAF(V600E) (n=2) or KRAS(G12D) (n=2), KRAS(G12V) or KRAS(G13D). DNA was obtained from both exocrine and endocrine components in seven cases, and the BRAF/KRAS status was identical in all cases. Split of the ALK locus was detected in a minority of tumor cells in two of eight cases, but EML4-ALK transcripts were absent. CONCLUSION: The association of an exocrine component in all cases and the similar profile of BRAF/KRAS mutations indicate that colorectal NEC may correspond to a high-grade transformation of colorectal carcinoma. New chemotherapy regimens using targeted therapies should be assessed in these tumors.